合理设计新自然分子的细菌导入系统。

IF 6.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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引用次数: 0

摘要

将新型化合物融入生物过程,对于改变或扩展现有的细胞功能具有巨大的潜力。然而,细胞对这些化合物的吸收往往受到选择性渗透膜的阻碍。我们介绍了一种新型细菌转运系统,该系统是为应对这一挑战而合理设计的。我们的方法利用了一种高度杂合的磺酸盐膜转运体,它允许以酰胺形式连接到磺丁酸转运载体分子上的货物分子进入细胞质。然后,这些货物可以通过γ-谷氨酰转移酶的工程变体从磺丁酰酰胺中卸载,该酶水解酰胺键并在细胞内释放货物分子。在这里,我们通过评估一系列结构不同的磺丁酰基酰胺,证明了该系统的两个组成部分都具有广泛的底物特异性。此外,我们还成功地在体内实现了合成摄取系统,并通过导入一种不渗透的非经典氨基酸展示了该系统的功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rational design of a bacterial import system for new-to-nature molecules

Rational design of a bacterial import system for new-to-nature molecules

Integration of novel compounds into biological processes holds significant potential for modifying or expanding existing cellular functions. However, the cellular uptake of these compounds is often hindered by selectively permeable membranes. We present a novel bacterial transport system that has been rationally designed to address this challenge. Our approach utilizes a highly promiscuous sulfonate membrane transporter, which allows the passage of cargo molecules attached as amides to a sulfobutanoate transport vector molecule into the cytoplasm of the cell. These cargoes can then be unloaded from the sulfobutanoyl amides using an engineered variant of the enzyme γ-glutamyl transferase, which hydrolyzes the amide bond and releases the cargo molecule within the cell. Here, we provide evidence for the broad substrate specificity of both components of the system by evaluating a panel of structurally diverse sulfobutanoyl amides. Furthermore, we successfully implement the synthetic uptake system in vivo and showcase its functionality by importing an impermeant non-canonical amino acid.

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来源期刊
Metabolic engineering
Metabolic engineering 工程技术-生物工程与应用微生物
CiteScore
15.60
自引率
6.00%
发文量
140
审稿时长
44 days
期刊介绍: Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.
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